Tremendous advance has been achieved for the transition-metal free coupling reactions induced by light these years, providing important strategies for the construction of C-N/S/P bonds, which was used frequently in the preparation of pharmaceutical drugs, agricultural products or materials and so on. In this review, the recent advance for the photo-induced coupling reactions for the construction of C-N/S/P bonds under transition-metal free conditions is reviewed.

Heterocyclic compounds are widely applied in medicine, fine chemical engineering and the related industrial fields. Consequently, the development of efficient strategies for heterocycle constructions continues to be of great appeal in organic synthesis. In recent years, the I2-catalyzed direct C-H bond functionalizations have emerged as one of the most efficient synthetic protocols to construct diverse heterocycles. In this review, the recent advances in I2-catalyzed C-H bond functionalizations by the types of C-C and C-N/O/S bond formations are summarized, and an outlook of this research filed is given.

Chiral aryl alcohols are prevalent in a broad range of biologically active compounds, pharmaceutical agents and natural products. They also constitute a broad class of optically active building blocks for the synthesis of important chiral compounds. In recent years, organoboron reagents are widely used in organic synthesis as they possess advantages of ready availability, low toxicity, good air and moisture stability as well as high functional group compatibility. Since the first report of rhodium-catalyzed asymmetric addition of aryl boronic acids to aryl aldehydes in 1998 by Miyaura, the use of organoboron reagents in asymmetric addition to various carbonyl compounds under various transition-metal catalyses has been intensively investigated. Over the past two decades, transition metal-catalyzed asymmetric addition of organoboron reagents to aldehydes and ketones has proved as one of the most direct and powerful methods for accessing versatile optically active alcohols. The development and progress of a wide range of chiral ligands for Rh, Ru, Pd, Ir, Cu, Ni and Co catalysis for asymmetric addition of organoboron reagents to aldehydes and ketones are summarized, and the achievements in enantioselective synthesis of chiral aryl alcohols and their applications in the synthesis of related biocative products are described. Among them, rhodium and ruthenium-catalyzed enantioselective additions have received considerable attention. In the cases of activated carbonyl compounds such as α-aryl ketoesters and α-diaryl diketones, excellent results can be attained in terms of both yield and enantioselectivity. However, it remains a daunting challenge for highly enantioselective addition to simple unactivated aldehydes and ketones owing to the difficulty in overcoming stereo differentiation. Future efforts in the community would focus on developing new effective transition-metal catalysts in addressing these issues by promoting efficient transformation and controlling excellent enantioselectivity.

Axially chiral biaryl skeletons are ubiquitous stuctural motifs that are widely represented in pharmaceuticals and natural products, and have been widely used as privileged chiral ligands/catalysts in asymmetric synthesis. Therefore, the asymmetric construction of these compounds has received tremendous attention. However, the established strategies are mainly limited to the construction of biaryls containing hexatomic aromatics, and the approaches towards atropisomers featuring pentatomic heteroaromatics connected through C-C or C-N bond have emerged gradually only until recently. The main hurdle is basically due to the increased distance of substituents ortho to the axis, which is responsible for lower barriers to rotation, thus rendering the asymmetric synthesis more challenging. This review summarizes recent advances on the enantioselective synthesis of atropisomers featuring pentatomic heteroaromatics.

Organosilicon compounds play an important role in pharmaceutical chemistry, material science and organic synthesis. Transition-metal-catalyzed direct silylation of C-H bond, as one of the most concise and efficient methods for the synthesis of organosilanes, has developed rapidly in recent years. In this paper, the recent advance in transition-metal-catalyzed silylation of C-H bonds since 2015 is mainly reviewed.

The multifunctional fluorescent probes can detect a plurality of anions and cations or other small molecules. These probes can greatly improve the detection efficiency and reduce the analysis cost with respect to the mono-analyte fluorescent probes. Thus, they have attracted much attention in recent years. According to their molecular structural characteristics, the reported multifunctional fluorescent probes are divided into three types as organic small molecules, polymers and metal-organic complexes. The new progress on their molecular design, synthesis and detecting application is reviewed on the viewpoint of sensing objects and performances. The developing potential of multifunctional fluorescent probes is envisioned also, and the probes capable of simultaneously identifying multiple analytes in the same system should be highlighted in the future

Maleimide, a common motif in a variety of natural alkaloids, has been extensively investigated due to its noteworthy biological activities and optical properties. Additionally, it can be transformed into many important heterocyclic frameworks such as succinimides, pyrrolidines, and 2-pyrrolidones. Thus, a great deal of attention has been focused on the development of new synthetic routes to access polyfunctionalized maleimides. In this article, the recent research progress in functionalization of double bond is reviewed based on maleimides according to Michael addition, oxidative coupling and cycloaddition reaction.

Pyrazole, an important class of nitrogen-containing five-member hetrocyclic compounds, widely exists in natural products, bio-active molecules and drugs, and it is also a valuable intermediate in organic synthesis. The synthesis of polysubstituted pyrazoles has attracted much attention and developed rapidly in recent years. Herein, the recent research progress in the construction of polysubstituted pyrazoles is summarized.

The cross dehydrogenation coupling reaction realizes direct coupling of two different X-H bonds to form a new chemical bond, thus featuring excellent step and atom economy. The traditional cross dehydrogenation coupling reaction was usually catalyzed by transition metal, which had the problems of expensive catalyst and serious pollution. Visible light-induced electron transfer is also an effective way to realize direct functionalization of X-H bonds. Visible-light-induced cross dehydrogenation coupling reaction under transition metal-free conditions is widely concerned due to the advantages of cleanliness, safety as well as high step and atom economy. Classified by the type of bonding, the research progress of these reactions is reviewed, and their future outlook is also discussed.

The development of efficient methods for the preparation of unnatural amino acids has long been an important goal since their widely application in synthetic and medicinal chemistry. The asymmetric α-functionalization of nucleophilic metalated azomethine ylides, which could be in situ-generated from readily-available aldimine esters, has been recogonized as a powerful strategy to synthesize unnatural amino acids. Over the past 20 years, tranistion metal-catalyzed asymmetric construction of unnatural amino acids using azomethine ylides have been extensively studied. In this review, the progress on metallated azomethine ylides invovled aymmetric transformation for the synthesis of unnatural amino acids is summarized according to eletrophilic reagents.

Carbazole and its derivatives are widely used in the field of medicine and photoelectric materials. A kind of stable cyclic hypervalent iodine reagents containing carbazole group was developed, which belong to benziodoxole compounds. In the presence of Cu(I) catalyst, these reagents reacted with aromatic substrates to give N-aryl carbazole derivatives. The reaction conditions are mild and suitable for a variety of electron-rich arenes. And a radical mechanism was proposed.

Compounds bearing difluoromethylthio (SCF2H) and monofluoromethylthio (SCFH2) groups are potentially important targets in the pharmaceutical and agrochemical fields due to their unique physical and chemical properties. The traditional methods of synthesizing these two kinds of compounds are difluoromethylation and monofluoromethylation of sulfhydryl substrates. However, the limitation of sulfhydryl substrates also limited the application and development of such compounds. Thus, it is still highly desirable to develop new methods for difluoromethylthiolation and monofluoromethylthiolation as well as new types of difluoromethylthiolation and monofluoromethylthiolation reagents. The recent development of direct difluoromethylthiolation and monofluoromethylthiolation reactions is summarized, and the related mechanism are also discussed.

N-O bond cleavage is one of the most efficient and powerful strategies to introduce N-or O-functional groups into molecules in organic synthesis. Copper catalyst, as the abundant in earth and inexpensive advantages has been widely used to construct C-N and C-O bond. Furthermore, N-O bond cleavage has been successfully applied in the total synthesis of natural products and pharmaceuticals. The new development of copper-catalyzed N-O bond cleavage and its application in the total synthesis of natural products and pharmaceuticals in recent years have been summarized.

Benzofulvenes were widely found in natural products and bioactive molecules, and also served as important building blocks in material science and transition-metal chemistry. Great efforts have been devoted to the efficient synthesis of these interesting molecules, and rapid advancement has been made in the past two decades. According to the types of the initiation of the reaction, these methods can roughly be classified into five categories:thermal or photochemical cyclization of enyne-al-lenes or enediynes, transition metal-catalyzed sequential cyclization reaction, electrophilic or nucleophilic attack initiated cyclization, radical initiated cyclization and acid promoted cyclization. This review describes the important synthetic methods of benzofulvenes according to their reaction types.

Quinoxalin-2(1H)-ones are very important N-heterocyclic moieties found in natural products and pharmaceuticals, and exhibit an amazingly wide spectrum of biological properties. Numerous efforts have been devoted to the development of efficient approaches for the C-H bond activation and functionalization of quinoxalin-2(1H)-ones in recent years, including alkylation, benzylation, acylation, arylation,amination, amidation, phosphonation, and fluoroalkylation. The recent advances in this area are summarized and their reaction mechanisms are discussed.

Asymmetric hydroformylation is one of the most important reactions for preparation of chiral aldehydes from alkenes. Recently, significant progress has been made in this field and a series of new ligands have been developed. Asymmetric hydroformylation of several important alkenes has been achieved, offering efficient and concise methods for the synthesis of chiral aldehydes. In this review, the achievements of asymmetric hydroformylation of typical alkenes and the development of ligands for asymmetric hydroformylation are summarized.

A nickel-catalyzed Negishi coupling of cyclobutanone oxime esters with aryl zinc reagents has been developed, in which nickel serves both as an initiator for imine radicals and a catalyst for the coupling of aryl zinc reagents with oxime esters. The protocol can avoid the use of poisonous cyanide and has broad substrate scope as well as good functional group compatibility. Therefore, this method provides an attractive strategy for the synthesis of valuable nitriles. Preliminary mechanistic studies indicate that a radical pathway is involved in the product formation.

α-Amino acids are the units of proteins, which not only widely occur in many biological important compounds and natural products, but also are useful as organic catalysts or ligands for asymmetric synthesis. Among them, glycines are particularly useful building blocks in organic synthesis. Direct C(sp3)-H bond functionalization of glycine derivatives provided an attractive synthesis strategy for the construction of a variety of α-substituted α-amino acids. The recent progress in the α-C(sp3)-H bond activation of glycine derivatives, with various reagents to form carbon-carbon and carbon-heteroatom bond, and oxidative coupling/cyclization reaction involving glycine derivatives is reviewed.

The C-H activation assisted by directing groups is an important measure for selective C-H activation at specific positions, and it is also one of the hot spots in the research field of organic chemistry. As an efficient directing group, carboxylic acid has the advantages of low cost, low toxicity, easy modification and using as traceless directing groups. Recent development on C-H functionalization directed by carboxyl group according to different coupling modes is summarized, and the representative reaction mechanism is briefly described. Existing problems with a brief outlook in this field are also presented.

The α-diazocarbonyl compounds are easy to prepare and can be dediazonized to highly reactive carbene intermediates under thermolytic or photolytic conditions. Chemical bonds can be efficiently constructed by carbene mediated reactions, including the insertion reaction of carbene into N-H bonds which is an effective method for constructing C-N bonds. The α-diazocarbonyl compounds have received extensive application in organic synthesis and pharmaceutical synthesis. The research progress in the insertion reaction of α-diazocarbonyl compounds into N-H bonds under transition metal, organic small molecules, biomacromolecule or photolytic and thermolytic conditions is summarized, including the reaction mechanism and synthesis applications. Finally, the prospects of this reaction are also discussed.

Aspirin (ASP), the first synthetic drug, is widely used as a non steroidal anti-inflammatory drug. It displays a variety of biological activities, such as anti-thrombosis, anti-inflammatory, anti-tumor, etc. A lot of works about the synthesis and related activity evaluation of its derivatives were reported. There are four kinds of derivatization methods:skeleton derivatization, prodrug derivatization, twin derivatization and metal coordination derivatization. According to the different modification sites, skeleton derivatization could be further divided into C(1)-COOH site modification, C(1)-COOH site and C(2)-OAc site simultaneous modification, C(2)-OAc site modification and benzene ring modification. NO-ASP is the main method to prepare antithrombotic derivatives, and metal coordination modification is the main synthesis scheme of anticancer derivatives. The structure modification and bioactivity research of aspirin in recent twenty years and the synthetic routes of 353 aspirin derivatives and the pharmacological activities of some derivatives are described, which provides a reference for the further development of aspirin derivatives.

The photocatalytic redox reactions have been widely concerned in organic chemistry due to their green, efficiency and safety. In this review, the cross-coupling/aromatization reactions are described based on photocatalytic organic hydrogen-evolution, which can be used to build organic carbon-carbon and carbon-heteroatom bonds by using a photocatalyst/catalyst dual catalytic system. Hydrogen is the only by-product in these reactions. The system and catalytic mechanisms of organic photocatalytic redox reaction are highlighted.

Based on the atomic economy, mild performance and environment friendly, the in-situ generation of hypervalent iodine reagents has been vastly applied in many significant oxidative reactions and asymmetric catalysis. In this paper, the progress of in-situ generated hypervalent iodine reagents is systematically reviewed, including conception and mechanisms. According to the different reaction types, the application of in-situ generated hapervalent iodine reagent in organic synthesis reaction is summarized, including trivalent iodine reagent, pentavalent iodine reagent and chiral hypervalent iodine reagent. The problem of in-situ generated hapervalent iodine researches is analyzed, and the future development of in-situ hapervalent iodine is prospected.

Indolines, an important class of heterocycles with a wide range of biological properties, are a key structural motif in numerous natural products and biologically active compounds. As a result, efficient methods for indolines synthesis have been the subject of extensive studies. In this review, recent studies on the synthesis of various functionalized indolines using unactivated alkenes are described. It involves radical addition/cyclization reaction in the presence of oxidizing agent, which is usually carried out under neutral reaction conditions using readily available oxidizing agents and different transition metals or under metal-free as catalysts.

Benzo five-/six-membered nitrogen-containing heterocyclic compound with a rigid plane and a large conjugate structure can emit characteristic fluorescence in a variety of organic solvents and mixed solutions, and N, O, S heteroatoms in the structure can serve as binding sites for fluorescent probes. Therefore, in recent years, benzo nitrogen-containing heterocyclic compounds are increasingly becoming one of the research focuses in the field of fluorescent probes. From the perspective of starting materials, synthesis methods, molecular structure, interaction mechanism, benzo five- / six-membered nitrogen-containing heterocyclic fluorescent probes containing the structure of benzoxazole, benzothiazole, benzimidazole, indole, carbazole, quinoline, benzopyrazine and phenazine are introduced with emphasis. And their detection application for a variety of analytes, such small molecules, metal cations, anions and pH are reviewed. In the future, it is worthy of further attention to the research on the integration of multiple heterocyclic functional structures into a multifunctional fluorescent probe by simple and green synthesis.

Small molecules (biological small molecules) in vivo are not only in a large number, involving inorganic small molecules, such as SO2, H2S, NO and CO, and more organic small molecules, such as monosaccharides, oligosaccharides, hormones, coenzymes, glycerol, stimulating factors, regulatory factors, Vitamins, etc., moreover, play an important role in pathology, physiology, and so on. Therefore, it is necessary to observe and monitor small molecules in vivo in real time, and the two-photon fluorescence probe is a necessary tool to achieve this goal. The advantages of two-photon fluorescence probe, such as fixed target (very small dot) excitation, high horizontal and vertical resolution, no photobleaching, no phototoxicity and deep imaging in tissues, and so on, demonstrate its unparalleled superiority. It can be used for dynamic 3D observation and monitoring of biological small molecules in cells or tissues. In this paper, CO, monosaccharide (glucose, β-galactosidase), SO2, H2S, NO, peroxy (sulfur) compounds, mercaptan/thiophenol, 1O2, formaldehyde, HNO, HclO, O2·- and ONOO- two-photon fluorescence probes which have been developed in recent 5 years were reviewed. The sensing mechanisms of these two-photon fluorescence probes were systematically analyzed, and the development and prospect of two-photon fluorescence probes for small biomolecules are prospected.

Tumor is one of the diseases with the highest mortality rate in the world. In view of the high risk and high mortality of tumor, researchers around the world are committed to develop more accurate and rapid diagnostic strategies and more effective treatments to fight tumor. Gradually, integrated optical diagnosis and treatment technologies for tumors have emerged. Fluoroboron fluorescein (BODIPY) has been widely used in tumor phototherapy because of its excellent optical properties. In this paper, BODIPY and its derivatives are introduced in detail as photosensitizers, photothermal transformants, and contrast agents in the diagnosis and treatment of tumors (photodynamic therapy, photothermal therapy, photoacoustic imaging) and integration of diagnosis and treatment. The effects of different BODIPY structures and their derivatives in tumor diagnosis and treatment were evaluated systematically. This is of great significance for the rational design of near-infrared BODIPY materials with high singlet oxygen quantum yield, high photothermal conversion, and good light stability and solubility.

Alkaline-earth metals continue to receive growing interest, as they are used as low-cost and non-toxic alternatives to transition-metals in various organic transformations. As ionic character and bond lengths increase along the row in the order Mg2+2+2+2+, bond energies decrease along the same row, the corresponding metal hydrides are apt to the formation of insoluble metal hydrides[AeH2]∞ (Ae=Mg, Ca, Sr, Ba) through Schlenk equilibrium in solution. Recently, a series of alkaline-earth metal hydrides stabilized by suitable ligands were discovered and characterized, and stoichiometric and catalytic reactions with small molecules were studied as well. In this paper, the recent progress in molecular alkaline-earth metal hydrides is reviewed.

A phosphine-mediated Staudinger/Aza-Michael addition of azides with trifluoromethyl substituted α,β-unsaturated ketones was developed, giving hydroamination products in medium to good yields (up to 96%). The hydroamination products could be prepared on gram scale and a wide range of substrates are tolerated under the optimized reaction conditions (30 examples). 31P NMR experiments indicate that this reaction was initiated by Staudinger reaction of azide with phosphine.

Water is a medium for reaction in living organisms, which is safe, cheap and easy to obtain, and visible light is a clean and renewable natural resource. Exploring the controllable free radical reaction under the illumination condition in water and developing a simple, green and efficient synthesis method not only conform to the current green chemistry theme, but also have an important scientific significance in theory and practical application. The classification and review of visible light catalysis in aqueous phase have been carried out in recent years, and the corresponding mechanisms are discussed.

A novel method of copper-catalyzed cyclization of 1-aryl-1-cycloalcohols and 1,3-dicarbonyl compounds has been developed, affording various cycloalkane-fused dihydrofurans in moderate to excellent yields. This transformation proceeds under mild conditions and with a good tolerance of functional groups. The mechanistic investigation revealed that the reaction involved radical intermediates.

Over the last decades, the transition metal-catalyzed cross-coupling reactions have become powerful organic synthetic methods for forming carbon-carbon and carbon-heteroatom bonds. Very recently, the introduction of visible light into transition metal catalysis opened a new avenue for achieving novel, highly enabling cross-coupling reactions that otherwise were elusive. This type of reaction has received extensive attention due to its simple, mild conditions and no need of photocatalyst. Based on the classification of transition metals, the research progress of transition metal-catalyzed cross-coupling reactions directly promoted by visible light is reviewed.

N-Benzyl is a common protecting group for organic amines, owing to its convenient and efficient removal. It plays an important role in organic synthesis, especially in the research of drugs and natural products. In recent years, a large number of researchers have conducted extensive studies on N-benzyl deprotection, but the related work is scattered and lacks systematic review. Therefore, the progress of N-benzyl removal is systematically and comprehensively summarized from the aspects of reductive, oxidative and acid-base debenzylation.

3-(5-Oxazolyl)indole-type natural products such as pimprinine and streptochlorin, widely exist in marine microorganism, because of their diverse biological activity, 3-(5-oxazolyl)indoles show good research and development potential in the field of medicine and pesticide. Numerous studies have been performed to synthesize 3-(5-oxazolyl)indole-type natural products, in which the construction of indole ring and oxazole ring is the most important part. In this paper, the reported natural products with 3-(5-oxazolyl)indole skeleton structure and their biological activities are summarized, and the synthetic methods for 3-(5-oxazolyl)indole skeleton and some of their mechanism are also reviewed. The application prospect of 3-(5-oxazol-yl)indole as a dominant active structure in the future was discussed.

Trifluoromethylation using Togni reagents usually releases one equivalent of iodobenzoats as wasteful byproducts. A visible-light-mediated, atom-and step-economical hydrotrifluoromethylation of aromatic alkynes and remote benzoyl-oxylation of α-C(sp3)-H bond of ether with Togni reagent as a bifunctional reagent by means of hydrogen atom transfer strategy was disclosed. The combination of two organic transformations into one reaction not only brings 100% atom economy but also addresses the challenge of stereoselective hydrotrifluoromethylation of aromatic alkynes. This unprecedented protocol offers an important access to a wide range of highly functionalized CF3-containing alkenes with great potential for post-modification.

Parvistemonine A was isolated from Stemona parviflora. The total synthesis of racemic parvistemonine A was completed in 6 steps for the first time, employing compound 7 as the starting material. The synthetic strategy features a tandem Friedel-Crafts cyclization and lactonization, Vilsmeier-Haack and Julia-Kocienski olefination. This study laid the foundation for the synthesis of the parvistemonine A derivative and its biological activity research.

Since the first tetrahydroisoquinoline alkaloid (THIQ), naphthyridinomycin, was found by Canadian scientist Kluepfel in 1974, nearly hundred members of this family have been reported. Such THIQ has attracted the research interest of many chemists and biologists due to its excellent biological activity and complex chemical structure. Especially, as an outstanding member of THIQ family, Ecteinascidin 743 (ET-743) has been commercialized in the European Union for the treatment of soft tissue tumors and ovarian cancer. Due to the extremely low content of natural products of bistetrahydroisoquinoline including ET-743 and the complexity of its chemical structure, the modification of its chemical structure has attracted more and more attention. Based on this, the recent advance in the synthesis of bistetrahydroisoquinoline analogues is reviewed.

Transition-metal-catalyzed Suzuki-Miyaura cross-coupling is one of the most powerful transformations for C-C biaryl bond formation at present. With the increasing demand for green chemistry, water as solvent for the Suzuki-Miyaura cross-coupling reactions has been of widespread interest. The literature in recent years on the Suzuki-Miyaura cross-coupling reactions by heterogeneous or homogeneous catalysis in water is reviewed, and their perspectives for further developments are also presented.